4-69098619-A-T

Variant names:

• chr4-69098619-A-T
• rs7438284
• NM_001074.4:c.801A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001074.4(UGT2B7):​c.801A>T​(p.Pro267Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,610,220 control chromosomes in the GnomAD database, including 209,131 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (25991 hom., cov: 30)
  • Exomes 𝑓: 0.49 (183140 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 33 publications found

Genes affected

UGT2B7 (HGNC:12554): (UDP glucuronosyltransferase family 2 member B7) The protein encoded by this gene belongs to the UDP-glycosyltransferase (UGT) family. UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This protein is localized in the microsome membrane, and has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ENSG00000299782 (HGNC:58802):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.613 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	NM_001074.4	MANE Select	c.801A>T	p.Pro267Pro	synonymous	Exon 2 of 6	NP_001065.2	P16662
	UGT2B7	NM_001330719.2		c.801A>T	p.Pro267Pro	synonymous	Exon 2 of 5	NP_001317648.1	E9PBP8
	UGT2B7	NM_001349568.2		c.54A>T	p.Pro18Pro	synonymous	Exon 3 of 7	NP_001336497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.801A>T	p.Pro267Pro	synonymous	Exon 2 of 6	ENSP00000304811.7	P16662
	UGT2B7	ENST00000868341.1		c.801A>T	p.Pro267Pro	synonymous	Exon 2 of 7	ENSP00000538400.1
	UGT2B7	ENST00000868343.1		c.801A>T	p.Pro267Pro	synonymous	Exon 2 of 7	ENSP00000538402.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 86867 AN: 150948 Hom.: 25945 Cov.: 30

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.564 AC: 140796 AN: 249522 AF XY: 0.554

Gnomad AFR exome AF: 0.714

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.704

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.494 AC: 720449 AN: 1459152 Hom.: 183140 Cov.: 54 AF XY: 0.495 AC XY: 359018 AN XY: 725794

African (AFR) AF: 0.716 AC: 23823 AN: 33292

American (AMR) AF: 0.713 AC: 31682 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 13264 AN: 26054

East Asian (EAS) AF: 0.703 AC: 27819 AN: 39564

South Asian (SAS) AF: 0.567 AC: 48646 AN: 85794

European-Finnish (FIN) AF: 0.578 AC: 30865 AN: 53388

Middle Eastern (MID) AF: 0.527 AC: 3036 AN: 5760

European-Non Finnish (NFE) AF: 0.459 AC: 510136 AN: 1110556

Other (OTH) AF: 0.517 AC: 31178 AN: 60280

GnomAD4 genome AF: 0.576 AC: 86968 AN: 151068 Hom.: 25991 Cov.: 30 AF XY: 0.584 AC XY: 43107 AN XY: 73760

African (AFR) AF: 0.712 AC: 29284 AN: 41148

American (AMR) AF: 0.659 AC: 10012 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1769 AN: 3454

East Asian (EAS) AF: 0.697 AC: 3542 AN: 5080

South Asian (SAS) AF: 0.604 AC: 2897 AN: 4800

European-Finnish (FIN) AF: 0.573 AC: 5994 AN: 10454

Middle Eastern (MID) AF: 0.581 AC: 165 AN: 284

European-Non Finnish (NFE) AF: 0.468 AC: 31635 AN: 67658

Other (OTH) AF: 0.586 AC: 1231 AN: 2100

Alfa AF: 0.497 Hom.: 6217

Bravo AF: 0.590

Asia WGS AF: 0.655 AC: 2275 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-0.61
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7438284; hg19: chr4-69964337; COSMIC: COSV59443167;